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目的:探讨喉鳞状细胞癌(laryngeal squamous cell carcinoma,LSCC)组织中N-myc下游调节基因1(N-myc downstream regulated gene 1,NDRG1)及NDRG2基因启动子甲基化状态和蛋白表达情况及其临床意义。方法:应用甲基化特异性PCR(methylation specific polymerase chain reaction,MSP)技术及免疫组织化学(immunohistochemestry,IHC)法检测45例LSCC组织、18例癌旁组织中NDRG1、NDRG2基因启动子区Cp G岛甲基化及蛋白表达情况,分析其与临床特征的关系。结果:LSCC组织中NDRG1及NDRG2基因启动子区的甲基化发生率显著高于癌旁正常组织[66.7%(30/45)vs 33.3%(6/18),53.3%(24/45)vs 22.2%(4/18),均P<0.05],其高甲基化与淋巴结转移及临床分期有关(P<0.05),与病理分级、临床分型、吸烟史、年龄和性别无关(P>0.05)。在LSCC组织中,NDRG1及NDRG2蛋白的阳性表达率显著低于癌旁组织[37.8%(17/45)vs 88.9%(16/18),33.3%(15/45)vs 83.3%(15/18),均P<0.01],其低蛋白表达与淋巴结转移及临床分期有关(P<0.05),与病理分级、临床分型、吸烟史、年龄和性别无关(P>0.05)。LSCC组织中NDRG1及NDRG2启动子区甲基化与其蛋白表达呈负相关(r1=-0.713,P<0.01;r2=-0.472,P<0.01)。结论:在LSCC组织中NDRG1及NDRG2基因均呈高甲基化及低蛋白表达状态,这可能与喉癌的发生和发展有关,NDRG1及NDRG2基因启动子区Cp G岛的异常甲基化可能是抑制它们蛋白表达的机制之一。
Objective: To investigate the promoter methylation status and protein expression of N-myc downstream regulated gene 1 (NDRG1) and NDRG2 in laryngeal squamous cell carcinoma (LSCC) Its clinical significance. Methods: 45 cases of LSCC tissues and 18 cases of paracancerous tissues were examined by methylation-specific polymerase chain reaction (MSP) and immunohistochemistry (IHC) Island methylation and protein expression, analysis of its relationship with clinical features. Results: The incidence of methylation of NDRG1 and NDRG2 in LSCC was significantly higher than that in adjacent normal tissues [66.7% (30/45) vs 33.3% (6/18), 53.3% (24/45 vs 22.2% (4/18), all P <0.05]. The hypermethylation was correlated with lymph node metastasis and clinical stage (P <0.05), but not with histological grade, clinical classification, smoking history, age and gender (P> 0.05) . The positive rates of NDRG1 and NDRG2 in LSCC tissues were significantly lower than those in paracancer tissues [37.8% (17/45) vs 88.9% (16/18), 33.3% (15/45) vs 83.3% (15/18) ), All P <0.01]. The low protein expression was correlated with lymph node metastasis and clinical stage (P <0.05), but not with histological grade, clinical classification, smoking history, age and sex (P> 0.05). Methylation of NDRG1 and NDRG2 in LSCC was negatively correlated with its protein expression (r1 = -0.713, P <0.01; r2 = -0.472, P <0.01). CONCLUSIONS: NDRG1 and NDRG2 genes are highly methylated and low-protein expressed in LSCC tissues, which may be related to the occurrence and development of laryngeal carcinoma. Aberrant methylation of CpG island in the promoter regions of NDRG1 and NDRG2 genes may be the main reason for their inhibition One of the mechanisms of protein expression.